Alterations in lung macrophage function after chronic hypoxia have not been clearly defined. In the present studies, we examined the effect of in vitro O2 depletion (PO2 approximately 15 mmHg) for as long as 96 h on lung macrophage endocytosis. In addition, we compared the effect of an acute decrease in O2 availability on endocytic function in lung macrophages maintained for 96 h under either aerobic or hypoxic conditions. Chronic hypoxia did not result in a decreased capacity for phagocytosis. In addition, in contrast to air-maintained cells, lung macrophages exposed to low PO2 for 96 h showed no impairment in phagocytic function during acute O2 depletion. Chronic hypoxia did produce a reversible impairment in pinocytosis. However, as with phagocytosis, pinocytosis in lung macrophages pre-exposed to low PO2 for 96 h was not decreased by acute hypoxia. In these in vitro studies, chronic hypoxia appeared to produce lung macrophage adaptations that served to maintain function, despite severe O2 depletion. These adaptations may be important with respect to pinocytic and phagocytic function in clinical conditions associated wtih sustained alveolar hypoxia.